How to solve this problem and others like it?

Alright, I think Steem might just be the perfect place to post a question like this given all the programmers and tech guys/gals and their complex algorithms.

I've been doing these math puzzles lately just for fun and to keep the mind sharp but I am legitimately stumped on this one. I've found a formula that works for 2/3 of the number sets but not all. It's usually the 4th number set that breaks it.

 I'm more interested in the thought process....

I'm not interested in the answer, I'm more interested in the thought process on how to solve something like this. I usually just guess and check until a formula works but I would love to know how a mathematician would tackle this as I know the guess and check method is not ideal. 

Let's see what you got!

Thanks for the help!!!!!

H2
H3
H4
3 columns
2 columns
1 column
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